Professor Roland Schuele from the University Women’s Hospital in Freiburg originally studied biochemistry. Nowadays, Schuele is researching the development of prostate cancer. During his scientific career, he has learnt that research cannot be steered in a particular direction. “It develops and we follow it,” said Schuele who has been able to gain astonishing insights into the molecular processes in tumour cells.
Androgens affect the gene activity in the prostate tumour cells and this causes the tumour to grow uncontrollably. For this reason, doctors often use androgen antagonists to treat prostate cancer. These are substances that inhibit the effect of androgens. However, this only works in about two thirds of patients; in one third of patients the tumour continues to grow for still unknown reasons and does so completely independently from the hormones. It even grows if it has no contact with the hormones. “In such cases, androgen antagonists do not help. And for these patients, there is no remedy available.”
Schuele’s research developed more quickly than expected; and it also went in a completely different direction than expected. And this research even seemed to offer a potential starting point for cancer therapy. Schuele found the enzyme LSD1 (lysine-specific demethylase 1) in the nuclei of prostate tumour cells, which affects the transcription of some genes. These genes are the same genes as those that are switched on by male sex hormones and whose uncontrollable activity drives the growth of the tumour. If this enzyme is blocked with a chemical inhibitor, then the tumour stops growing. At least, this is the result of initial experiments carried out with isolated tumour cells. And the principle functions independently of the presence of androgens. “This raises hopes that there exists a potential to use such inhibitors to treat cancer patients who have ceased to respond to androgen antagonists,” said Schuele.
His insights were also groundbreaking in a more theoretical respect. The enzyme LSD1 is what is referred to as an epigenetic factor. Such factors can activate or silence DNA stretches by attaching or removing small molecules. This leaves a signature for transcription enzymes, which determines which proteins the cell finally produces. Initially, it was assumed that the signature was rigid and remained the same until the death of the cell. “This was for a long time the central dogma of epigenetics,” said Schuele whose results however show that the contrary is the case; that this signature is very dynamic and changes repeatedly.In the meantime, approximately 30 epigenetic factors have been found that are similar to the enzyme discovered by Schuele. The new research area has developed rapidly and a completely new field has opened up for the pharmaceutical industry. In 2004 within a few months, Schuele received three offers from other universities to head up their institutes. But the Freiburg Women’s Hospital did not want to let him go and offered him something even better. Schuele accepted and is curious to find out what kind of discoveries he will make in the future. It is impossible to predict in research. Research develops gradually and scientists follow the discoveries. And this is something that never ceases to fascinate him.
Further information:Prof. Dr. rer. nat. Roland SchueleUniversity Women's Hospital and Centre for Clinical ResearchUniversity of FreiburgBreisacherstrasse 6679106 FreiburgTel.: +49 (0)761/270-6310Fax: +49 (0)761/270-6311E-mail: roland.schuele(at)uniklinik-freiburg.de